Project 1 """"""""Determinants of disease progression and role of latent infection in transmission"""""""" will study a series of factors that will help understanding why only a limited number of individuals infected with Leishmania donovani develop Visceral Leishmaniasis (VL) on the Indian subcontinent. Project 1 will also contribute to assess the role of asymptomatically infected individuals (those who do not progress to disease) in L. donovani transmission. This project will combine field and laboratory work. Two serological surveys of leishmaniasis infection will be done in high transmission areas to identify recent asymptomatic seroconvertors and controls in the study area (see Core C for details). Similariy, VL cases and controls (i.e healthy household contacts) will also be identified and included in the different studies. Project 1 is divided in 4 specific aims.
Aim 1 will examine the association of HLA-type with seroconversion and disease progression controlling for several confounders identified in the previous risk factor studies.
Aim 2 will use a recently developed quantitative PCR to assess parasite load in different subpopulations (i.e.seroconvertors and seronegative individuals) and assess its influence in progression to VL taking into account genetic and environmental factors.
Aim 3 will examine the association between co-infections with other Neglected Tropical Diseases (NTD) and VL in two case-control studies. (1) An unmatched case-control study comparing Leishmania seropositives with the general population and (2) a matched case-control study comparing VL cases to community controls will be used to assess the effect of filaria- or geo-helminths-L. donovani co-infection on progression to VL. Finally, Aim 4 will contribute to study the role of asymptomatically infected persons by (1) validating a modified SLA-based Quantiferon to detect cellular immune response in asymptomatic individuals and (2) selecting individuals (peripheral blood mononuclear cells (PBMC) culture positive) to be included in the xenodiagnosis experiments (see Project 2 for details) .
Results generated in this project will be of importance for individual as well as for public health. Identifying risk factors for progression from VL infection to disease may allow for secondary prevention. Evidence on the potential role of asymptomatic infections in L. donovani transmission may have major implications for the current VL control strategy.
|Singh, Neetu; Kumar, Rajiv; Engwerda, Christian et al. (2016) Tumor necrosis factor alpha neutralization has no direct effect on parasite burden, but causes impaired IFN-Î³ production by spleen cells from human visceral leishmaniasis patients. Cytokine 85:184-90|
|Sudarshan, Medhavi; Singh, Toolika; Singh, Bhawana et al. (2016) Suppression of host PTEN gene expression for Leishmania donovani survival in Indian visceral leishmaniasis. Microbes Infect 18:369-72|
|Sharma, Smriti; Davis, Richard E; Srivastva, Shweta et al. (2016) A Subset of Neutrophils Expressing Markers of Antigen-Presenting Cells in Human Visceral Leishmaniasis. J Infect Dis 214:1531-1538|
|Montes de Oca, Marcela; Kumar, Rajiv; de Labastida Rivera, Fabian et al. (2016) Blimp-1-Dependent IL-10 Production by Tr1 Cells Regulates TNF-Mediated Tissue Pathology. PLoS Pathog 12:e1005398|
|Singh, Om Prakash; Singh, Bhawana; Chakravarty, Jaya et al. (2016) Current challenges in treatment options for visceral leishmaniasis in India: a public health perspective. Infect Dis Poverty 5:19|
|Singh, Om Prakash; Hasker, Epco; Boelaert, Marleen et al. (2016) Elimination of visceral leishmaniasis on the Indian subcontinent. Lancet Infect Dis 16:e304-e309|
|Sundar, Shyam; Singh, Anup (2016) Recent developments and future prospects in the treatment of visceral leishmaniasis. Ther Adv Infect Dis 3:98-109|
|Faleiro, Rebecca J; Kumar, Rajiv; Bunn, Patrick T et al. (2016) Combined Immune Therapy for the Treatment of Visceral Leishmaniasis. PLoS Negl Trop Dis 10:e0004415|
|Singh, Om Prakash; Sundar, Shyam (2015) Developments in Diagnosis of Visceral Leishmaniasis in the Elimination Era. J Parasitol Res 2015:239469|
|Ghosh, Prakash; Hasnain, Md Golam; Ghosh, Debashis et al. (2015) A comparative evaluation of the performance of commercially available rapid immunochromatographic tests for the diagnosis of visceral leishmaniasis in Bangladesh. Parasit Vectors 8:331|
Showing the most recent 10 out of 78 publications